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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2003-10-10
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pubmed:databankReference |
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pubmed:abstractText |
Distinct posttranslational modifications on histones occur in specific patterns to mediate certain chromosomal events. For example, on histone H3, phosphorylation at Ser10 can enhance GCN5-mediated Lys14 acetylation to promote transcription. To gain insight into the mechanism underlying this synergism, we determined the structure of Tetrahymena GCN5 (tGCN5) and coenzyme A (CoA) bound to unmodified and Ser10-phosphorylated 19 residue histone H3 peptides (H3p19 and H3p19Pi, respectively). The tGCN5/CoA/H3p19 structure reveals that a 12 amino acid core sequence mediates extensive contacts with the protein, providing the structural basis for substrate specificity by the GCN5/PCAF family of histone acetyltransferases. Comparison with the tGCN5/CoA/H3p19Pi structure reveals that phospho-Ser10 and Thr11 mediate significant histone-protein interactions, and nucleate additional interactions distal to the phosphorylation site. Functional studies show that histone H3 Thr11 is necessary for optimal transcription at yGcn5-dependent promoters requiring Ser10 phosphorylation. Together, these studies reveal how one histone modification can modulate another to affect distinct transcriptional signals.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1097-2765
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
461-73
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:14536085-Acetylation,
pubmed-meshheading:14536085-Acetyltransferases,
pubmed-meshheading:14536085-Amino Acid Sequence,
pubmed-meshheading:14536085-Animals,
pubmed-meshheading:14536085-Crystallography, X-Ray,
pubmed-meshheading:14536085-Dose-Response Relationship, Drug,
pubmed-meshheading:14536085-Histone Acetyltransferases,
pubmed-meshheading:14536085-Histones,
pubmed-meshheading:14536085-Kinetics,
pubmed-meshheading:14536085-Models, Biological,
pubmed-meshheading:14536085-Models, Chemical,
pubmed-meshheading:14536085-Models, Molecular,
pubmed-meshheading:14536085-Molecular Sequence Data,
pubmed-meshheading:14536085-Mutation,
pubmed-meshheading:14536085-Phosphorylation,
pubmed-meshheading:14536085-Protein Binding,
pubmed-meshheading:14536085-Protein Structure, Secondary,
pubmed-meshheading:14536085-Single-Strand Specific DNA and RNA Endonucleases,
pubmed-meshheading:14536085-Substrate Specificity,
pubmed-meshheading:14536085-Tetrahymena,
pubmed-meshheading:14536085-Threonine,
pubmed-meshheading:14536085-Transcription, Genetic
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pubmed:year |
2003
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pubmed:articleTitle |
Structural basis for histone and phosphohistone binding by the GCN5 histone acetyltransferase.
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pubmed:affiliation |
The Wistar Institute, Philadelphia, PA 19104, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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